CN111686159A

CN111686159A - New application of malus asiatica composition preparation in preparation of anti-breast cancer drugs

Info

Publication number: CN111686159A
Application number: CN202010602061.0A
Authority: CN
Inventors: 韦飞燕; 张艳华; 刘春明; 韦金燕; 唐满姣; 张伟
Original assignee: Huahong Pharmaceutical Co ltd Guangxi Zhuang Autonomous Region
Current assignee: Huahong Pharmaceutical Co ltd Guangxi Zhuang Autonomous Region
Priority date: 2019-06-28
Filing date: 2020-06-28
Publication date: 2020-09-22
Also published as: CN110237131A; CN111686158A

Abstract

The invention relates to the technical field of traditional Chinese medicines, and provides a new application of a crab apple composition preparation in preparation of an anti-breast cancer medicine. The crab apple composition is prepared from the following medicines in parts by weight: 1000-5000 parts of tasselflower herb, 500-6600 parts of spreading hedyotis herb, 1000-5000 parts of radix rose malloti, 500-6600 parts of mallotus root, 500-6600 parts of pennycress, 1000-7500 parts of suberect spatholobus stem and 1000-5000 parts of downy rosemyrtle root. The Chinese patent medicine safflower composition preparation has good inhibition effect on breast cancer cells, provides a theoretical basis for new application of old medicines, and provides a new idea for developing the anti-cancer effect of the safflower composition.

Description

New application of malus asiatica composition preparation in preparation of anti-breast cancer drugs

Technical Field

The invention relates to the technical field of traditional Chinese medicines, in particular to a new application of a crab apple composition preparation in preparing an anti-breast cancer medicine.

Background

The Malus asiatica composition preparation is a Chinese patent medicine, mainly comprises Emilia, herba Hedyotidis Diffusae, radix Urenae Lobatae, radix Malloti Apeltae, herba Thlaspis, caulis Spatholobi and radix Rhodomyrti, has the effects of clearing away heat and toxic materials, eliminating dampness and stopping leukorrhagia, removing blood stasis and relieving pain, and can be used for treating leukorrhagia and menoxenia caused by damp-heat stagnation, with symptoms of leukorrhagia, yellow and thick urine, lower abdomen vague pain, lumbosacral pain and abdominal pain during menstruation; chronic pelvic inflammatory disease, adnexitis, endometritis with the above syndromes.

Herba Duchesneae Indicae, dry whole plant of Emilia sonchifolia (L.) DC. of Compositae (origin: Mass Standard of Zhuang nationality of Guangxi autonomous region (first volume)). Vertical root, erect stem, no hair or short hair, grayish green. Has effects of clearing away heat and toxic materials, promoting urination, and treating urinary system infection, pharyngolaryngitis, and sore. Alias: red-back leaf, sowthistle tasselflower herb, wild agaric vegetable, red-head grass, underleaf red and purple-back leaf.

Oldenlandia diffusa, dried whole herb of Hedyotis diffusa willd, rubiaceae (source: Zhu Yao quality standard (first volume) in the autonomous region of Guangxi Zhuang nationality). Height of 15-50cm, slender root, branch, and white flower. The stem is somewhat square or flat cylindrical, smooth and hairless, with multiple branches emanating from the base. Its patent medicine is bitter and bland in taste and cold in nature. The main effects are clearing away heat and toxic material, inducing diuresis and reducing edema. It is especially good at treating various types of inflammation. In clinical practice, the compatibility of oldenlandia diffusa is found to be proper, which can cure various diseases. Alias: herba Hedyotidis Diffusae, herba Clerodendranthi Spicati, herba Mesonae chinensis, herba Hedyotidis Diffusae, herba Serpentis , and herba Hedyotidis Diffusae.

Radix seu fructus Heteropanacis Delavayi, dry aerial parts of L. of Urena lobata L. of Malvaceae, California procumbens (from the first volume of Zhuang-nationality medicine quality Standard in the autonomous region of Guangxi province). The rose mallow is distributed in the south of the Yangtze river in China. The peach blossom with coarse leaf is distributed in southwest and Fujian, Guangdong, Guangxi, etc. Has the effects of dispelling wind, promoting diuresis, promoting blood circulation, relieving swelling, and clearing away heat and toxic materials. It is commonly used for common cold, arthralgia due to wind-dampness, dysentery, diarrhea, stranguria, leukorrhagia, menoxenia, swelling and pain due to traumatic injury, pharyngitis, acute mastitis, skin sore, furuncle, and snake bite.

Root of divaricate Gynura, root of divaricate Clerodendrum, root of common Clerodendrum and root of Chinese medicinal materials. Is dried root and rhizome of Mallotus apelta (Lour.) of Euphorbiaceae (source: quality standard of Zhuang autonomous region Zhuang medicine 2017) of Muell. Is distributed in Shaanxi, Jiangsu, Anhui, Zhejiang, Jiangxi, Fujian, Henan, Hunan, Guangxi, Guangdong, Hainan, Guizhou, Yunnan and other places. Has the effects of clearing away heat, promoting diuresis, relieving depletion, and removing blood stasis. It is commonly used for hepatitis, enteritis, stranguria with turbid discharge, leukorrhagia, rectocele, metroptosis, hepatosplenomegaly, traumatic injury and sprain.

Thlaspi arvense, a dry aerial part of Thlaspi arvense L. of the plant Thlaspi arvense of the family Brassicaceae (source: part of the 2015 edition of Chinese pharmacopoeia); the stem is upright, not branched or branched, and has edges. The whole herb can be used as medicine, has the effects of clearing liver and improving vision, regulating the middle warmer and promoting diuresis, detoxifying and reducing swelling, and is mainly used for treating nephritis and endometritis.

Caulis Spatholobi, the dried rattan of Spatholobus suberectus Dunn of Leguminosae (origin: the first part of the Chinese pharmacopoeia 2015 edition), perennial vines, which are wild in mountain valley forests and mountain shrubs, are mainly produced in Guangdong, Guangxi, Yunnan and other areas. The dried rattan is used as a traditional Chinese medicine for promoting blood circulation and enriching blood, and the medicinal history is long. Researches show that the caulis Spatholobi extract, total flavone and chemical components contained in the caulis Spatholobi extract have various pharmacological activities including influence on blood circulation system, anti-tumor, antivirus, antioxidation, etc. The stem used as a medicine is one of the main sources of the traditional Chinese medicine caulis spatholobi, and has the effects of promoting blood circulation, enriching blood, regulating menstruation, relieving pain, relaxing tendons and activating collaterals. It can be used for treating soreness of waist and knees, numbness, paralysis, and menoxenia.

The root of Myrtus communis (dried root of Rhodomyrtus tomentosa (Aiton) Hasskal of Myrtaceae (source: quality Standard for Zhuang nationality autonomous region Zhuang medicine in Guangxi, 2017) is mainly distributed in Guangdong, Guangxi, Fujian, Yunnan, etc. Contains chemical components such as phenols and tannin, and has sweet, astringent and mild properties. Has inhibitory effect on Staphylococcus aureus. Can be administered both topically and orally, and has effects of regulating qi-flowing, relieving pain, promoting diuresis, relieving diarrhea, removing blood stasis, stopping bleeding, invigorating kidney, and nourishing blood. Can be used for treating hepatitis, rheumatalgia, lumbar muscle strain, metrorrhagia, etc.

At present, the application of the safflower composition preparation for treating breast cancer is not reported in documents at home and abroad.

Disclosure of Invention

The invention aims to provide a new application of a safflower composition preparation in preparing an anti-breast cancer medicament.

The composition is prepared from the following medicines in parts by weight: 1000-5000 parts of tasselflower herb, 500-6600 parts of spreading hedyotis herb, 1000-5000 parts of radix rose malloti, 500-6600 parts of mallotus root, 500-6600 parts of pennycress, 1000-7500 parts of suberect spatholobus stem and 1000-5000 parts of downy rosemyrtle root.

The composition further comprises at least one pharmaceutically acceptable excipient.

The composition can be made into tablet, granule, capsule, decoction, oral liquid, dripping pill, soft capsule or powder.

1. Due to the adoption of the technical scheme, compared with the prior art, the inventor finds that the known Chinese patent medicine Huahong composition preparation has a good inhibition effect on breast cancer cells. And the safflower composition preparation is a finished product medicine on the market, has higher probability of being applied to a human body, and has good clinical development prospect. The invention has wide material source, low cost and ideal use effect.

2. The medicine of the present invention has certain curative effect on treating tumor and less toxic side effect.

3. Has analgesic effect, and can relieve cancer pain and improve life quality of patients.

4. Pharmacological test research shows that the safflower composition extract has certain inhibition effect on human breast cancer cells MCF-7 and can inhibit the growth of mouse transplanted tumor.

Detailed Description

The following examples are further illustrative, but the present invention is not limited to these examples.

Example 1

1. The raw materials comprise: 1250g of tassel flower, 750g of spreading hedyotis herb, 1250g of rose mallow, 750g of mallotus root, 750g of pennycress, 1000g of suberect spatholobus stem, 1250g of downy rosemyrtle root, 10g of hydroxypropyl methyl cellulose, 20g of talcum powder, 10g of magnesium stearate and 130g of silicon dioxide.

2. The preparation method comprises the following steps: taking 300g of emilia sonchifolia, crushing into fine powder, adding six types of emilia sonchifolia, mallotus apelta, herba pennycress, downy roseus and caulis spatholobi, decocting with water for two times, namely 2 hours for the first time and 1.5 hours for the second time, combining decoction, filtering, concentrating the filtrate into clear paste with the relative density of 1.18-1.23 (80 ℃), adding ethanol until the ethanol content reaches 65%, stirring uniformly, standing for 24 hours, filtering, recovering the ethanol from the filtrate under reduced pressure, concentrating the filtrate into thick paste with the relative density of 1.25-1.30 (80 ℃), drying, crushing into fine powder, adding an appropriate amount of auxiliary materials, mixing uniformly, preparing into granules, drying, pressing into 1000 tablets, and coating sugar coat or film to obtain 1000 tablets.

Example 2

1. The raw materials comprise: 1667g of tassel, 1000g of spreading hedyotis herb, 1667g of rose mallow flower, 1000g of mallotus root, 1000g of pennycress, 1333g of suberect spatholobus stem, 1667g of downy rosemyrtle root, 120g of starch, 20g of microcrystalline cellulose and 20g of magnesium stearate.

2. The preparation method comprises the following steps: adding water into seven medicinal materials of emilia sonchifolia, oldenlandia diffusa, rose mallow, mallotus root, pennycress, downy rosemyrtle root and suberect spatholobus stem for extraction twice, carrying out 2 hours for the first time and 1.5 hours for the second time, merging decoction, filtering, concentrating filtrate to obtain clear paste with the relative density of 1.18-1.23 (80 ℃), adding ethanol until the ethanol content reaches 65%, uniformly stirring, standing for 24 hours, filtering, recovering ethanol from filtrate under reduced pressure, concentrating to obtain thick paste with the relative density of 1.20-1.25 (60 ℃), carrying out spray drying granulation, and filling into capsules to obtain 1000 granules.

Example 3

1. The raw materials comprise: 5000g of tassel flower, 3000g of spreading hedyotis herb, 5000g of rose mallow flower, 3000g of mallotus root, 3000g of pennycress, 4000g of suberect spatholobus stem, 5000g of downy rosemyrtle root, 3580g of starch and 20g of steviosin.

2. The preparation method comprises the following steps: seven medicinal materials including herba Emiliae, herba Hedyotidis Diffusae, radix Urenae Lobatae, radix Malloti Apeltae, herba Thlaspis, radix Rhodomyrti and caulis Spatholobi are decocted with water twice, 2 hours for the first time and 1.5 hours for the second time, the decoction is combined and filtered, the filtrate is concentrated to relative density of 1.20(80 ℃), ethanol is added until the ethanol content reaches 65%, the mixture is stirred uniformly, the mixture is kept stand for 24 hours, the filtrate is filtered, the ethanol is recovered under reduced pressure and concentrated to thick paste with relative density of 1.25-1.30 (80 ℃), a proper amount of starch and steviosin are added, the mixture is mixed uniformly, prepared into particles, dried and packaged into 1000 bags.

Example 4

1. The raw materials comprise: 3334g of tassel, 2000g of spreading hedyotis herb, 3334g of rose mallow, 2000g of mallotus root, 2000g of pennycress, 2666g of suberect spatholobus stem, 3334g of downy rosemyrtle root, 500g of soybean oil and 190g of beeswax.

2. The preparation method comprises the following steps: decocting seven medicinal materials including herba Emiliae, herba Hedyotidis Diffusae, radix Urenae Lobatae, radix Malloti Apeltae, herba Thlaspis, caulis Spatholobi and radix Rhodomyrti twice with water, wherein the amount of water added for the first time is 10 times of the total weight of the medicinal materials, the amount of water added for the second time is 8 times of the total weight of the medicinal materials, the decocting time is 1.5 hours, filtering is carried out, vacuum drying and concentrating the filtrate until the relative density is 1.20(80 ℃) to obtain clear paste, adding 3-6% of gelatin solution (the concentration is 5%) of the clear paste amount until no precipitate is generated, standing for 3-5 hours, filtering is carried out, adding ethanol into the filtrate until the ethanol content is 65%, standing and filtering are carried out, carrying out vacuum concentration on the filtrate until the relative density is 1.28(80 ℃) to obtain thick paste, carrying out spray drying at 45-55 ℃; heating and stirring soybean oil and beeswax to obtain uniform liquid, cooling to room temperature, then mixing with 310g of the extracted active ingredients, stirring uniformly, passing through a colloid mill, and subpackaging in soft capsules to obtain a soft capsule product.

Example 5

1. The raw materials comprise: 3500g of tassel, 4000g of spreading hedyotis herb, 2000g of rose mallow, 4000g of mallotus root, 4000g of pennycress, 5000g of suberect spatholobus stem, 3000g of downy rosemyrtle root and 3g of saccharin sodium.

2. The preparation method comprises the following steps: decocting seven medicinal materials including herba Emiliae, herba Hedyotidis Diffusae, radix Urenae Lobatae, radix Malloti Apeltae, herba Thlaspis, caulis Spatholobi and radix Rhodomyrti with water in an amount which is 20 times of the weight of the raw materials, wherein the decocting time is 3.5 hours, 2 hours for the first time and 1.5 hours for the 2 nd time, filtering, vacuum-drying and concentrating the filtrate to a relative density of 1.18-1.23 (80 ℃) to obtain a fluid extract, adding ethanol to reach an ethanol content of 75%, standing, filtering, and concentrating the filtrate under reduced pressure to a thick paste with a relative density of 1.25-1.30 (80 ℃) to obtain 850g of active ingredients for later use. Adding 850g of extracted active ingredients into saccharin sodium, adding distilled water to 10L, stirring uniformly, standing, filtering, filling, and sterilizing to obtain an oral liquid product.

Example 6

1. The raw materials comprise: 1000g of tassel, 6600g of oldenlandia diffusa, 1000g of rose mallow, 6600g of mallotus root, 500g of pennycress, 7500g of suberect spatholobus stem, 1000g of downy rosemyrtle root, 140g of starch, 30g of microcrystalline cellulose and 20g of magnesium stearate.

Example 7

1. The raw materials comprise: 5000g of tassel, 500g of spreading hedyotis herb, 5000g of rose mallow, 500g of mallotus root, 6600g of pennycress, 1000g of suberect spatholobus stem, 5000g of downy rosemyrtle root, 130g of starch, 30g of microcrystalline cellulose and 30g of magnesium stearate.

Experimental example 1 anti-tumor in vitro experiment of the composition preparation of Malus asiatica

Cell lines: human breast cancer cells (MCF-7).

Preparing mother liquor: ultrasonic extracting the contents of the flower red tablet (example 1), the flower red capsule (example 2) and the flower red granule (example 3) with 95% methanol for 30min, concentrating and drying to obtain crude extract. The crude extract was dissolved in DMSO to prepare a 20mg/mL stock solution to be assayed.

The test method comprises the following steps: MTT method is used for detecting the proliferation inhibition effect of the crude extracts of the safflower tablets, the safflower granules and the safflower capsules on human breast cancer MCF-7 cells. Specifically, MCF-7 cells in the logarithmic growth phase were digested with 0.25% trypsin, seeded into 96-well plates at a concentration of 5000 cells per well, 100 μ L per well, and 100 μ L of test solutions (2000, 1000, 500, 250, 125, 62.5ug/mL) at different concentrations were added after 24h, and culture solutions containing DMSO at the corresponding concentrations were used as solvent controls. After the test compound is applied for 48 hours, 20. mu.L of MTT is added to each well, and the mixture is further placed into a cell culture box for culture. After 4h, the supernatant was discarded, 150. mu.L of DMSO was added to each well, and the mixture was shaken on a horizontal shaker for 1min at low speed. The absorbance (A) of each well was then measured at a wavelength of 570nm using a microplate reader, and the cell viability was calculated.

The survival rate of the cells is 100 percent (A control group-A medicine group)/A control group is multiplied by 100 percent

The cell survival rate under different concentrations of the test compound can be obtained according to the formula, and a cell survival rate-concentration curve is drawn according to the cell survival rate-concentration curve, so that the concentration of the different test compounds for inducing 50% of apoptosis, namely an IC50 value, is obtained.

And (3) test results: as shown in Table 1, the IC50 value of the crude extract of the safflower carthamus tablet on MCF-7 cells is 1.68 +/-0.17 mg/ml, the IC50 value of the crude extract of the capsule of the safflower on MCF-7 cells is 1.53 +/-0.24 mg/ml, and the IC50 value of the crude extract of the granule of the safflower on MCF-7 cells is 1.50 +/-0.22 mg/ml.

And (4) test conclusion: through molecular biological tests, it can be seen that the crude extract of the crab apple composition shows obvious cytotoxic activity on human breast cancer cells (MCF-7). Therefore, the crude extracts of the safflower tablets and the safflower capsules have certain inhibition effect on human breast cancer cells (MCF-7) in vitro.

TABLE 1 results of cytotoxicity test (IC) of Huahong composition preparation against human mammary cancer₅₀Value, mg/ml)

	Crude extract of safflower	Crude extract of Huahong capsule	Crude extract of Malus asiatica granules
				Human breast cancer cell (MCF-7)	1.68±0.17	1.53±0.24	1.50±0.22

Claims

1. The novel application of the Malus asiatica composition preparation in preparing the anti-breast cancer drugs is that the raw material drugs of the traditional Chinese medicine composition comprise Emilia, herba Hedyotidis Diffusae, radix Urenae Lobatae, radix Malloti Apeltae, herba Thlaspis, caulis Spatholobi and downy Rosemyrtle root.

2. The new use as claimed in claim 1, wherein the said composition is prepared from the following drugs in parts by weight: 1000-5000 parts of tasselflower herb, 500-6600 parts of spreading hedyotis herb, 1000-5000 parts of radix rose malloti, 500-6600 parts of mallotus root, 500-6600 parts of pennycress, 1000-7500 parts of suberect spatholobus stem and 1000-5000 parts of downy rosemyrtle root.

3. The new use as claimed in claim 2, characterized in that said composition further comprises at least one pharmaceutically acceptable adjuvant.

4. The new use as claimed in claim 1 or 2, wherein the composition is in the form of tablet, granule, capsule, decoction, oral liquid, drop pill, soft capsule or powder.